This is a resubmission of 2 R01 DA12828 06, "Cognitive Neuropsychology of HIV and Drug Abuse," a program of theory driven research designed to test the hypothesis that HIV infection significantly increases vulnerability to neurobehavioral complications among substance dependent-individuals (SDIs).We propose that certain neurocognitive deficits, such as abnormalities of inhibition and reward processing, will be present among both HIV+ and HIV- SDIs compared with persons with no history of drug dependence. Additionally, HIV+ SDIs will show deficits in nondeclarative learning and memory, functions dependent on the integrity of neostriatum, a subcortical region typically affected prominently by HIV; HIV- SDIs are expected to show some level of impairment in nondeclarative learning but of lesser severity compared with HIV+ SDIs. We propose to move forward with the following primary goals: 1) we will compare HIV+ and matched HIV- SDIs on carefully chosen measures of response inhibition, impulsive choice, and procedural learning; 2) we will recruit and test two control groups of HIV+ and HIV- persons with no history of drug dependence in order to address the potential unique and synergistic effects of a positive HIV serostatus with a history of substance dependence; 3) we will examine the association of these neurocognitive functions with indices of critical daily and social functions. 4) we will develop and pilot test an MRI protocol for investigating structural brain integrity among HIV+ and HIV- persons with and without a history of substance dependence. Our model has considerable potential utility as a first step toward study of HIV-specific effects on brain function in the context of the more non-specific cognitive effects of drug dependence, an area in which research is lacking. The translational and public health relevance of these studies includes the potential for development of more effective clinical neuropsychological measures for assessment of HIV+ and HIV- SDIs; development of indices with relevance to employment, continued risk behavior and adherence with medication; predicting which cognitive deficits observed might be more likely to remit with abstinence from drugs; and development of a framework for evaluating and perhaps distinguishing response to treatment of substance dependence among HIV+ and HIV-infected SDIs. [unreadable] [unreadable] [unreadable]